References

nogr

Экспериментальная и клиническая гастроэнтерология

Experimental and Clinical Gastroenterology

1682-8658

«Global Media Technologies»

10.31146/1682-8658-ecg-216-8-141-150

nogr-2416

Research Article

ОБЗОР

REVIEW

Фармакодинамические и фармакокинетические особенности комбинированного применения глицирризиновой кислоты

Pharmacodynamic and pharmacokinetic aspects of combined use of glycyrrhizinic acid

https://orcid.org/0000-0002-4690-1811

Приходько

В. А.

Prikhodko

V. A.

noemail@neicon.ru

https://orcid.org/0000-0003-4294-5531

Оковитый

С. В.

Okovityi

S. V.

sergey.okovity@pharminnotech.com

Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской ФедерацииРоссияSaint Petersburg State Chemical and Pharmaceutical UniversityRussian Federation

Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской Федерации; Научно-клинический и образовательный центр гастроэнтерологии и гепатологии, федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный университет»РоссияSaint Petersburg State Chemical and Pharmaceutical University; Saint Petersburg State UniversityRussian Federation

2023

09102023

08141150

2023

Приходько В.А., Оковитый С.В.

Prikhodko V.A., Okovityi S.V.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.nogr.org/jour/article/view/2416

Глицирризиновая кислота - соединение тритерпеновой природы растительного происхождения, обладающее антистеатозной, антицитолитической, противовоспалительной, антифибротической, антихолестатической, а также антиапоптотической, антинеопластической и другими видами активности. Результаты недавних исследований показывают, что помимо гепатопротекторного действия, глицирризиновая кислота способна к образованию надмолекулярных самоассоциатов и мицелл, что придает ей свойства фармакокинетического, а следовательно, и фармакодинамического энхансера. Таким образом, перспективы и возможности комбинированного применения глицирризиновой кислоты при заболеваниях печени и других органов обусловлены, с одной стороны, фармакотерапевтическими свойствами самой молекулы, а с другой - ее особенностями как формообразующего вещества. Настоящий обзор посвящен фармакодинамическим и фармакокинетическим аспектам применения глицирризиновой кислоты в комбинациях с эссенциальными фосфолипидами и урсодезоксихолевой кислотой.

Glycyrrhizinic acid is a triterpenoid plant-derived compound with potent antisteatotic, anticytolitic, anti-inflammatory, antifibrotic, anticholestatic as well as antiapoptotic, antineoplastic and some other effects. Recent studies have demonstrated glycyrrhizinic acid to form supramolecular self-associates and micelles, which makes it a pharmacokinetic, and, hence, a pharmacodynamic enhancer. Thus, the prospects and possibilities of combined use of glycyrrhizinic acid in liver disease and other pathologies arise due to the pharmacological properties of the molecule itself as well as its function as drug carrier and delivery enhancer. The present review is focused on the pharmacodynamic and pharmacokinetic features of glycyrrhizinic acid combinations with essential phospholipids and ursodeoxycholic acid.

глицирризиновая кислотаэссенциальные фосфолипидыурсодезоксихолевая кислотагепатопротекторызаболевания печенифармакокинетика

glycyrrhizinic acidessential phospholipidsursodeoxycholic acidhepatoprotective agentsliver diseasepharmacokinetics

References1

Li J.Y., Cao H. Y., Liu P., Cheng G. H., Sun M. Y. Glycyrrhizic acid in the treatment of liver diseases: literature review. Biomed Res Int. 2014;2014:872139. doi: 10.1155/2014/872139

Yan T., Wang H., Cao L., et al. Glycyrrhizin Alleviates Nonalcoholic Steatohepatitis via Modulating Bile Acids and Meta-Inflammation. Drug Metab Dispos. 2018;46(9):1310-1319. doi: 10.1124/dmd.118.082008

Li X., Sun R., Liu R. Natural products in licorice for the therapy of liver diseases: Progress and future opportunities. Pharmacol Res. 2019;144:210-226. doi: 10.1016/j.phrs.2019.04.025

Abo El-Magd N.F., El-Mesery M., El-Karef A., El-Shishtawy M. M. Glycyrrhizin ameliorates high fat diet-induced obesity in rats by activating NrF2 pathway. Life Sci. 2018;193:159-170. doi: 10.1016/j.lfs.2017.11.005.

Lingappan K. NF-κB in Oxidative Stress. Curr Opin Toxicol. 2018;7:81-86. doi: 10.1016/j.cotox.2017.11.002.

Hu C.C., Chen W. K., Liao P. H., Yu W. C., Lee Y. J. Synergistic effect of cadmium chloride and acetaldehyde on cytotoxicity and its prevention by quercetin and glycyrrhizin. Mutat Res. 2001;496(1-2):117-127. doi: 10.1016/s1383-5718(01)00214-5.

Mollica L., De Marchis.F, Spitaleri A., et al. Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem Biol. 2007;14(4):431-441. doi: 10.1016/j.chembiol.2007.03.007.

Zhao F., Fang Y., Deng S., et al. Glycyrrhizin Protects Rats from Sepsis by Blocking HMGB1 Signaling. BioMed Res Int. 2017;2017:9719647. doi: 10.1155/2017/9719647.

Rashedinia M., Saberzadeh J., Khosravi Bakhtiari T., Hozhabri S., Arabsolghar R. Glycyrrhizic Acid Ameliorates Mitochondrial Function and Biogenesis Against Aluminum Toxicity in PC12 Cells. Neurotox Res. 2019;35(3):584-593. doi: 10.1007/s12640-018-9967-2.

Tang Q., Cao Y., Xiong W., et al. Glycyrrhizic acid exerts protective effects against hypoxia/reoxygenation-induced human coronary artery endothelial cell damage by regulating mitochondria. Exp Ther Med. 2020;20(1):335-342. doi: 10.3892/etm.2020.8668.

Teng L., Kou C., Lu C., et al. Involvement of the ERK pathway in the protective effects of glycyrrhizic acid against the MPP+-induced apoptosis of dopaminergic neuronal cells.Int J Mol Med. 2014;34(3):742-748. doi: 10.3892/ijmm.2014.1830.

Wang D., Guo T. Q., Wang Z. Y., et al. ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells. Braz J Med Biol Res. 2014;47(9):773-779. doi: 10.1590/1414-431x20143760.

Sun X,. Duan X., Wang C., et al. Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease in mice [published correction appears in Eur J Pharmacol. 2022 Aug 5;928:175106]. Eur J Pharmacol. 2017;806:75-82. doi: 10.1016/j.ejphar.2017.04.021.

Okovity S.V., Prikhodko V. A., Bezborodkina N. N., Kudryavtsev B. N. Hepatoprotectors. Moscow. GEOTAR-Media. 2022.@@ Оковитый С. В., Приходько В. А., Безбородкина Н. Н., Кудрявцев Б. Н. Гепатопротекторы. М: ГЭОТАР-Медиа. 2022.

Tian Q., Zhang C. N., Wang X. H., et al. Glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles for liver-targeted delivery. Biomaterials. 2010;31(17):4748-4756. doi: 10.1016/j.biomaterials.2010.02.042.

Tian G., Pan R., Zhang B., et al. Liver-Targeted Combination Therapy Basing on Glycyrrhizic Acid-Modified DSPE-PEG-PEI Nanoparticles for Co-delivery of Doxorubicin and Bcl-2 siRNA. Front Pharmacol. 2019;10:4. doi: 10.3389/fphar.2019.00004.

Sun Y., Dai C., Yin M., Lu J., Hu H., Chen D. Hepatocellular carcinoma-targeted effect of configurations and groups of glycyrrhetinic acid by evaluation of its derivative-modified liposomes.Int J Nanomedicine. 2018;13:1621-1632. Published 2018 Mar 16. doi: 10.2147/IJN.S153944.

Wu F., Xue H., Li X., et al. Enhanced targeted delivery of adenine to hepatocellular carcinoma using glycyrrhetinic acid-functionalized nanoparticles in vivo and in vitro. Biomed Pharmacother. 2020;131:110682. doi: 10.1016/j.biopha.2020.110682.

Mirza M.U., Mirza A. H., Ghori N. U., Ferdous S. Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson’s disease: a pharmacoinformatics study. Drug Des Devel Ther. 2014;9:187-198. doi: 10.2147/DDDT.S72794.

Chintharlapalli S., Papineni S., Jutooru I., McAlees A., Safe S. Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor {gamma} agonists in colon cancer cells. Mol Cancer Ther. 2007;6(5):1588-1598. doi: 10.1158/1535-7163.MCT-07-0022.

Ruan Z., Orozco I. J., Du J., Lü W. Structures of human pannexin 1 reveal ion pathways and mechanism of gating. Nature. 2020;584(7822):646-651. doi: 10.1038/s41586-020-2357-y.

Tang C., Ding H., Sun Y., Han Z., Kong L. A narrative review of COVID-19: magnesium isoglycyrrhizinate as a potential adjuvant treatment. Ann Palliat Med. 2021;10(4):4777-4798. doi: 10.21037/apm-20-1971.

Ploeger B., Mensinga T., Sips A., Seinen W., Meulenbelt J., DeJongh J. The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. Drug Metab Rev. 2001;33(2):125-147. doi: 10.1081/dmr-100104400.

Dufour J.F., Caussy C., Loomba R.Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges. Gut. 2020;69(10):1877-1884. doi: 10.1136/gutjnl-2019-319104.

Prikhodko V.A., Bezborodkina N. N., Okovityi S. V. Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. Biomedicines. 2022;10(2):274. doi: 10.3390/biomedicines10020274.

Okovityi S.V., Raikhelson K. L., Prikhodko V. A.Combined hepatoprotective pharmacotherapy for liver disease. Exp Clin Gastroenterol. 2022;203(7):5-20. (In Russ.) doi: 10.31146/1682-8658-ecg-203-7-5-20.@@ Оковитый С. В., Райхельсон К. Л., Приходько В. А. Комбинированная гепатопротекторная фармакотерапия заболеваний печени. Экспериментальная и клиническая гастроэнтерология. 2022;203(7):5-20. doi: 10.31146/1682-8658-ecg-203-7-5-20.

Selyutina O. Yu., Apanasenko I. E., Polyakov N. E. Membrane-modifying activity of glycyrrhizic acid.Russ Chem Bull. 2015;64:1555-1559.

Selyutina O. Yu., Apanasenko I. E., Kim A. V., et al. Spectroscopic and molecular dynamics characterization of glycyrrhizin membrane-modifying activity. Colloids and Surfaces B: Biointerfaces, 2016;147:459-466.

Selyutina O. Yu., Polyakov N. E., Korneev D. V., Zaitsev B. N. Drug Deliv. 2016;23:848-855.

Selyutina O. Yu., Apanasenko I. E., Shilov A. G., Khalikov S. S., Polyakov N. E.Russ Chem Bull. 2017;66:129-135.

Glazachev Y.I., Schlotgauer A. A., Timoshnikov V. A., et al. J Membrane Biol. 2020;253:343-356.

Selyutina O.Y., Shelepova E. A., Paramonova E. D., Kichigina L. A., Khalikov S. S., Polyakov N. E. Glycyrrhizin-induced changes in phospholipid dynamics studied by 1H NMR and MD simulation. Arch Biochem Biophys. 2020;686:108368. doi: 10.1016/j.abb.2020.108368.

Zelikman M.V., Kim A. V., Medvedev N. N. et al. Structure of dimers of glycyrrhizic acid in water and their complexes with cholesterol: Molecular dynamics simulation. J Struct Chem. 2015;56:67-76. doi: 10.1134/S0022476615010102.

Selyutina O. Yu., Kononova P. A., Polyakov N. E.Russ Chem Bull. 2021;70(12):2434-2439.

Bailly C., Vergoten G. Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?. Pharmacol Ther. 2020;214:107618. doi: 10.1016/j.pharmthera.2020.107618.

Kim A.V., Shelepova E. A., Evseenko V. I., Dushkin AV., Medvedev N. N., Polyakov N. E. Mechanism of the enhancing effect of glycyrrhizin on nifedipine penetration through a lipid membrane. J Mol Liq. 2021;344:117759. doi: 10.1016/j.molliq.2021.117759.

Kim A.V., Shelepova E. A., Selyutina O. Y., et al. Glycyrrhizin-Assisted Transport of Praziquantel Anthelmintic Drug through the Lipid Membrane: An Experiment and MD Simulation. Mol Pharm. 2019;16(7):3188-3198. doi: 10.1021/acs.molpharmaceut. 9b00390.

Yang F.H., Zhang Q., Liang Q. Y., et al. Bioavailability enhancement of paclitaxel via a novel oral drug delivery system: paclitaxel-loaded glycyrrhizic acid micelles. Molecules. 2015;20(3):4337-4356. doi: 10.3390/molecules20034337.

Kong R., Zhu X., Meteleva E. S., et al. Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes.Int J Pharm. 2017;534(1-2):108-118. doi: 10.1016/j.ijpharm.2017.10.011.

Meteleva E.S., Chistyachenko Yu.S., Suntsova L. P., et al. Disodium salt of glycyrrhizic acid - A novel supramolecular delivery system for anthelmintic drug praziquantel. J Drug Deliv Sci Technol. 2019;50:66-77. doi: 10.1016/j.jddst.2019.01.014.

Tolstikova T.G., Khvostov M. V., Bryzgalov A. O. The complexes of drugs with carbohydrate-containing plant metabolites as pharmacologically promising agents. Mini Rev Med Chem. 2009;9(11):1317-1328. doi: 10.2174/138955709789878123.

Selyutina O.Y., Polyakov N. E. Glycyrrhizic acid as a multifunctional drug carrier - From physicochemical properties to biomedical applications: A modern insight on the ancient drug.Int J Pharm. 2019;559:271-279. doi: 10.1016/j.ijpharm.2019.01.047.

Varlamova A.I., Arkhipov I. A. Biological activity of fenbendazole based on supramolecular delivery system with disodium salt of glycyrrhizic acid. Agricultural Biol. 2020;55(4):830-842. (In Russ.) doi: 10.15389/agrobiology.2020.4.830eng.@@ Варламова А. И., Архипов И. А. Биологическая активность фенбендазола на основе супрамолекулярной системы доставки с динатриевой солью глицирризиновой кислоты. Сельскохозяйственная биология. 2020;55(4):830-842. doi: 10.15389/agrobiology.2020.4.830eng.

Dajani A.I., Popovic B. Essential phospholipids for nonalcoholic fatty liver disease associated with metabolic syndrome: A systematic review and network meta-analysis. World J Clin Cases. 2020;8(21):5235-5249. doi: 10.12998/wjcc.v8.i21.5235.

Aleynik S.I., Leo M. A., Takeshige U., Aleynik M. K., Lieber C. S. Dilinoleoylphosphatidylcholine is the active antioxidant of polyenylphosphatidylcholine. J Investig Med. 1999;47(9):507-512.

Poniachik J., Baraona E., Zhao J., Lieber C. S. Dilinoleoylphosphatidylcholine decreases hepatic stellate cell activation. J Lab Clin Med. 1999;133(4):342-348. doi: 10.1016/s0022-2143(99)90064-1.

Mak K.M., Wen K., Ren C., Lieber C. S. Dilinoleoylphosphatidylcholine reproduces the antiapoptotic actions of polyenylphosphatidylcholine against ethanol-induced hepatocyte apoptosis [published correction appears in Alcohol Clin Exp Res. 2003 Jul;27(7):1212]. Alcohol Clin Exp Res. 2003;27(6):997-1005. doi: 10.1097/01.ALC.0000071901.62432.09.

Leuschner F., Wagener H. H., Neumann B. Die antihyperlipämische und antiatherogene Wirksamkeit der “essentiellen” Phospholipide (EPL) im pharmakologischen Versuch [The anti-hyperlipemic and anti-atherogenic effect of “essential” phospholipids: a pharmacologic trial]. Arzneimittelforschung. 1976;26(9a):1743-1772.

Ipatova O.M., Torkhovskaia T. I., Kniazhev V. A., et al. Tormozhenie s pomoshch’iu novogo gepato-protektornogo preparata “fosfoliv” razvitiia khronicheskogo gepatita u krys [Use of a novel hepato-protective preparation “phospholiv” for inhibition of development of chronic hepatitis in rats]. Vopr Med Khim. 1998;44(6):537-543. (in Russ.)

Khan M.S., Krishnaraj K. Phospholipids: a novel adjuvant in herbal drug delivery systems. Crit Rev Ther Drug Carrier Syst. 2014;31(5):407-428. doi: 10.1615/critrevtherdrugcarriersyst.2014010634.

Medvedeva N.V., Prosorovskiy V. N., Ignatov D. V., et al. Biomed Khim. 2015;61(2):219-230. (in Russ.) doi: 10.18097/PBMC20156102219.

Wang H., Cui Y., Fu Q., et al. A phospholipid complex to improve the oral bioavailability of flavonoids. Drug Dev Ind Pharm. 2015;41(10):1693-1703. doi: 10.3109/03639045.2014.991402.

Kuche K., Bhargavi N., Dora C. P., Jain S. Drug-Phospholipid Complex-a Go Through Strategy for Enhanced Oral Bioavailability. AAPS PharmSciTech. 2019;20(2):43. doi: 10.1208/s12249-018-1252-4.

Paumgartner G., Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002;36(3):525-531. doi: 10.1053/jhep.2002.36088.

Milani M. Ursodeoxycholic Acid (UDCA) in Biliary Diseases: A Clinical Review. Br J Med Med Res. 2014;4(9): 1783-1790.

Payen L., Sparfel L., Courtois A., Vernhet L., Guillouzo A., Fardel O. The drug efflux pump MRP2: regulation of expression in physiopathological situations and by endogenous and exogenous compounds. Cell Biol Toxicol. 2002;18(4):221-233. doi: 10.1023/a:1016020626941.

Okada K., Shoda J., Taguchi K., et al. Ursodeoxycholic acid stimulates Nrf2-mediated hepatocellular transport, detoxification, and antioxidative stress systems in mice. Am J Physiol Gastrointest Liver Physiol. 2008;295(4): G735-G747. doi: 10.1152/ajpgi.90321.2008.

Amaral J.D., Viana R. J., Ramalho R. M., Steer C. J., Rodrigues C. M. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res. 2009;50(9):1721-1734. doi: 10.1194/jlr.R900011-JLR200.

Ko W.K., Lee S. H., Kim S. J., et al. Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages. PLoS One. 2017;12(6): e0180673. doi: 10.1371/journal.pone.0180673.

Keely S.J., Steer C. J., Lajczak-McGinley N. K. Ursodeoxycholic acid: a promising therapeutic target for inflammatory bowel diseases?. Am J Physiol Gastrointest Liver Physiol. 2019;317(6): G872-G881. doi: 10.1152/ajpgi.00163.2019.

Rodrigues C.M., Fan G., Ma X., Kren B. T., Steer C. J. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest. 1998;101(12):2790-2799. doi: 10.1172/JCI1325.

The authors declare that there are no conflicts of interest present.